Abstract Chronic pain affects approximately 100 million Americans, a number that is projected to increase over the next several decades. Chronic pain represents a negative affective state that promotes the transition from recreational, limited intake to alcohol dependence and excessive alcohol drinking. Acutely, alcohol produces analgesia in humans, and 25% of chronic pain patients and 79% of high-risk alcohol drinkers use alcohol to manage their pain. We have shown that acute alcohol administration attenuates increased pain sensitivity (or allodynia) in our rodent model of chronic inflammatory pain, and that the analgesic effects of alcohol may shift over the course of chronic pain. However, there is a gap in knowledge regarding the neurobiological mechanisms underlying the analgesic effects of alcohol in the context of chronic pain. The basolateral amygdala (BLA) plays an important role in various pain processes, including pain chronification and the regulation of pain-associated negative affect. Chronic pain increases BLA spontaneous and evoked activity and cFos mRNA expression, and our preliminary data suggest that alcohol dependence and withdrawal induces a state of increased pain sensitivity due to a similar increase in BLA activity. The endocannabinoid system (eCB) is well known for mediating analgesia, and we have shown that alcohol withdrawal-induced pain avoidance behavior is associated with a potential decrease in eCB tone within the BLA. The main research objective of the current proposal is to investigate the role of BLA activation and endocannabinoid signaling in the analgesic effects of acute alcohol. The studies outlined in this proposal will test the predictions that: 1) acute alcohol activates BLA interneurons in the context of chronic inflammatory pain and that activation of these neurons are necessary for the analgesic effects of alcohol, and 2) that acute alcohol will increase BLA endocannabinoids and that inhibition of the endocannabinoid catabolic enzyme monoacylglycerol lipase (MAGL) will rescue increases in pain-like behavior in a manner similar to that of acute alcohol administration. In addition to filling a gap in knowledge regarding the neurobiology underlying the relationship between chronic pain and alcohol, this proposal will provide a promising future biomedical science PhD with vital research training to become an independent scientist in the field of alcohol research.